Gomez-Cambronero Julian
Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University School of Medicine, Dayton, Ohio 45435.
J Biol Chem. 2014 Aug 15;289(33):22557-22566. doi: 10.1074/jbc.R114.574152. Epub 2014 Jul 2.
Phospholipase D (PLD) enzymes play a double vital role in cells: they maintain the integrity of cellular membranes and they participate in cell signaling including intracellular protein trafficking, cytoskeletal dynamics, cell migration, and cell proliferation. The particular involvement of PLD in cell migration is accomplished: (a) through the actions of its enzymatic product of reaction, phosphatidic acid, and its unique shape-binding role on membrane geometry; (b) through a particular guanine nucleotide exchange factor (GEF) activity (the first of its class assigned to a phospholipase) in the case of the mammalian isoform PLD2; and (c) through protein-protein interactions with a wide network of molecules: Wiskott-Aldrich syndrome protein (WASp), Grb2, ribosomal S6 kinase (S6K), and Rac2. Further, PLD interacts with a variety of kinases (PKC, FES, EGF receptor (EGFR), and JAK3) that are activated by it, or PLD becomes the target substrate. Out of these myriads of functions, PLD is becoming recognized as a major player in cell migration, cell invasion, and cancer metastasis. This is the story of the evolution of PLD from being involved in a large number of seemingly unrelated cellular functions to its most recent role in cancer signaling, a subfield that is expected to grow exponentially.
磷脂酶D（PLD）在细胞中发挥着双重重要作用：它们维持细胞膜的完整性，并参与细胞信号传导，包括细胞内蛋白质运输、细胞骨架动力学、细胞迁移和细胞增殖。PLD在细胞迁移中的特殊作用是通过以下方式实现的：（a）通过其反应酶产物磷脂酸的作用及其对膜几何形状的独特形状结合作用；（b）在哺乳动物异构体PLD2的情况下，通过特定的鸟嘌呤核苷酸交换因子（GEF）活性（其所属类别中第一个被指定为磷脂酶的活性）；（c）通过与广泛的分子网络进行蛋白质-蛋白质相互作用：威斯科特-奥尔德里奇综合征蛋白（WASp）、Grb2、核糖体S6激酶（S6K）和Rac2。此外，PLD与多种被其激活的激酶（蛋白激酶C、FES、表皮生长因子受体（EGFR）和JAK3）相互作用，或者PLD成为靶底物。在这些众多的功能中，PLD正逐渐被认为是细胞迁移、细胞侵袭和癌症转移中的主要参与者。这就是PLD从参与大量看似不相关的细胞功能到其在癌症信号传导中最新作用的演变故事，癌症信号传导这一领域预计将呈指数级增长。
